Propagation of tau pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies (original) (raw)

References

1. Ahmed Z, Cooper J, Murray TK, Garn K, McNaughton E, Clarke H, Parhizkar S, Ward MA, Cavallini A, Jackson S, Bose S, Clavaguera F, Tolnay M, Lavenir I, Goedert M, Hutton ML, O’Neill MJ (2014) A novel in vivo model of tau propagation with rapid and progressive neurofibrillary tangle pathology: the pattern of spread is determined by connectivity, not proximity. Acta Neuropathol 127:667–683. doi:10.1007/s00401-014-1254-6
   Article PubMed PubMed Central CAS Google Scholar
2. Ahmed Z, Josephs KA, Gonzalez J, DelleDonne A, Dickson DW (2008) Clinical and neuropathologic features of progressive supranuclear palsy with severe pallido-nigro-luysial degeneration and axonal dystrophy. Brain 131:460–472. doi:10.1093/brain/awm301
   Article PubMed Google Scholar
3. Allen B, Ingram E, Takao M, Smith MJ, Jakes R, Virdee K, Yoshida H, Holzer M, Craxton M, Emson PC, Atzori C, Migheli A, Crowther RA, Ghetti B, Spillantini MG, Goedert M (2002) Abundant tau filaments and nonapoptotic neurodegeneration in transgenic mice expressing human P301S tau protein. J Neurosci 22:9340–9351 (pii: 22/21/9340)
   PubMed CAS Google Scholar
4. Andorfer C, Acker CM, Kress Y, Hof PR, Duff K, Davies P (2005) Cell-cycle reentry and cell death in transgenic mice expressing nonmutant human tau isoforms. J Neurosci 25:5446–5454. doi:10.1523/JNEUROSCI.4637-04.2005
   Article PubMed CAS Google Scholar
5. Andreadis A, Brown WM, Kosik KS (1992) Structure and novel exons of the human tau gene. Biochemistry 31:10626–10633
   Article PubMed CAS Google Scholar
6. Arendt T (2004) Neurodegeneration and plasticity. Int J Dev Neurosci 22:507–514. doi:10.1016/j.ijdevneu.2004.07.007
   Article PubMed CAS Google Scholar
7. Aronov S, Aranda G, Behar L, Ginzburg I (2002) Visualization of translated tau protein in the axons of neuronal P19 cells and characterization of tau RNP granules. J Cell Sci 115:3817–3827
   Article PubMed CAS Google Scholar
8. Asuni AA, Boutajangout A, Quartermain D, Sigurdsson EM (2007) Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements. J Neurosci 27:9115–9129. doi:10.1523/JNEUROSCI.2361-07.2007
   Article PubMed CAS Google Scholar
9. Bi M, Ittner A, Ke YD, Gotz J, Ittner LM (2011) Tau-targeted immunization impedes progression of neurofibrillary histopathology in aged P301L tau transgenic mice. PLoS One 6:e26860. doi:10.1371/journal.pone.0026860
   Article PubMed PubMed Central CAS Google Scholar
10. Binder LI, Frankfurter A, Rebhun LI (1985) The distribution of tau in the mammalian central nervous system. J Cell Biol 101:1371–1378
    Article PubMed CAS Google Scholar
11. Bohnen NI, Warner MA, Kokmen E, Beard CM, Kurland LT (1994) Prior blood transfusions and Alzheimer’s disease. Neurology 44:1159–1160
    Article PubMed CAS Google Scholar
12. Boluda S, Iba M, Zhang B, Raible KM, Lee VM, Trojanowski JQ (2015) Differential induction and spread of tau pathology in young PS19 tau transgenic mice following intracerebral injections of pathological tau from Alzheimer’s disease or corticobasal degeneration brains. Acta Neuropathol 129:221–237. doi:10.1007/s00401-014-1373-0
    Article PubMed PubMed Central CAS Google Scholar
13. Boutajangout A, Ingadottir J, Davies P, Sigurdsson EM (2011) Passive immunization targeting pathological phospho-tau protein in a mouse model reduces functional decline and clears tau aggregates from the brain. J Neurochem 118:658–667. doi:10.1111/j.1471-4159.2011.07337.x
    Article PubMed PubMed Central CAS Google Scholar
14. Boutajangout A, Quartermain D, Sigurdsson EM (2010) Immunotherapy targeting pathological tau prevents cognitive decline in a new tangle mouse model. J Neurosci 30:16559–16566. doi:10.1523/JNEUROSCI.4363-10.2010
    Article PubMed PubMed Central CAS Google Scholar
15. Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259
    Article PubMed CAS Google Scholar
16. Braak H, Del Tredici K (2011) Alzheimer’s pathogenesis: is there neuron-to-neuron propagation? Acta Neuropathol 121:589–595. doi:10.1007/s00401-011-0825-z
    Article PubMed CAS Google Scholar
17. Braak H, Del Tredici K, Schultz C, Braak E (2000) Vulnerability of select neuronal types to Alzheimer’s disease. Ann N Y Acad Sci 924:53–61
    Article PubMed CAS Google Scholar
18. Braak H, Thal DR, Ghebremedhin E, Del Tredici K (2011) Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol 70:960–969. doi:10.1097/NEN.0b013e318232a379
    Article PubMed CAS Google Scholar
19. Brion JP, Hanger DP, Bruce MT, Couck AM, Flament-Durand J, Anderton BH (1991) Tau in Alzheimer neurofibrillary tangles. N- and C-terminal regions are differentially associated with paired helical filaments and the location of a putative abnormal phosphorylation site. Biochem J 273(Pt 1):127–133
    Article PubMed PubMed Central CAS Google Scholar
20. Bruce ME, McBride PA, Jeffrey M, Scott JR (1994) PrP in pathology and pathogenesis in scrapie-infected mice. Mol Neurobiol 8:105–112. doi:10.1007/BF02780660
    Article PubMed CAS Google Scholar
21. Buee L, Delacourte A (1999) Comparative biochemistry of tau in progressive supranuclear palsy, corticobasal degeneration, FTDP-17 and Pick’s disease. Brain Pathol 9:681–693
    Article PubMed CAS Google Scholar
22. Calafate S, Buist A, Miskiewicz K, Vijayan V, Daneels G, de Strooper B, de Wit J, Verstreken P, Moechars D (2015) Synaptic contacts enhance cell-to-cell tau pathology propagation. Cell Rep 11:1176–1183. doi:10.1016/j.celrep.2015.04.043
    Article PubMed CAS Google Scholar
23. Callahan CA, Thomas JB (1994) Tau-beta-galactosidase, an axon-targeted fusion protein. Proc Natl Acad Sci USA 91:5972–5976
    Article PubMed PubMed Central CAS Google Scholar
24. Chai X, Wu S, Murray TK, Kinley R, Cella CV, Sims H, Buckner N, Hanmer J, Davies P, O’Neill MJ, Hutton ML, Citron M (2011) Passive immunization with anti-Tau antibodies in two transgenic models: reduction of Tau pathology and delay of disease progression. J Biol Chem 286:34457–34467. doi:10.1074/jbc.M111.229633
    Article PubMed PubMed Central CAS Google Scholar
25. Chakrabarty P, Hudson Iii VJ, Sacino AN, Brooks MM, D’Alton S, Lewis J, Golde TE, Giasson BI (2015) Inefficient induction and spread of seeded tau pathology in P301L mouse model of tauopathy suggests inherent physiological barriers to transmission. Acta Neuropathol. doi:10.1007/s00401-015-1444-x
    Google Scholar
26. Clavaguera F, Bolmont T, Crowther RA, Abramowski D, Frank S, Probst A, Fraser G, Stalder AK, Beibel M, Staufenbiel M, Jucker M, Goedert M, Tolnay M (2009) Transmission and spreading of tauopathy in transgenic mouse brain. Nat Cell Biol 11:909–913. doi:10.1038/ncb1901
    Article PubMed PubMed Central CAS Google Scholar
27. Clavaguera F, Lavenir I, Falcon B, Frank S, Goedert M, Tolnay M (2013) “Prion-like” templated misfolding in tauopathies. Brain Pathol 23:342–349. doi:10.1111/bpa.12044
    Article PubMed CAS Google Scholar
28. Collinge J, Palmer MS, Sidle KC, Hill AF, Gowland I, Meads J, Asante E, Bradley R, Doey LJ, Lantos PL (1995) Unaltered susceptibility to BSE in transgenic mice expressing human prion protein. Nature 378:779–783. doi:10.1038/378779a0
    Article PubMed CAS Google Scholar
29. Crary JF, Trojanowski JQ, Schneider JA, Abisambra JF, Abner EL, Alafuzoff I, Arnold SE, Attems J, Beach TG, Bigio EH, Cairns NJ, Dickson DW, Gearing M, Grinberg LT, Hof PR, Hyman BT, Jellinger K, Jicha GA, Kovacs GG, Knopman DS, Kofler J, Kukull WA, Mackenzie IR, Masliah E, McKee A, Montine TJ, Murray ME, Neltner JH, Santa-Maria I, Seeley WW, Serrano-Pozo A, Shelanski ML, Stein T, Takao M, Thal DR, Toledo JB, Troncoso JC, Vonsattel JP, White CL 3rd, Wisniewski T, Woltjer RL, Yamada M, Nelson PT (2014) Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol 128:755–766. doi:10.1007/s00401-014-1349-0
    Article PubMed PubMed Central CAS Google Scholar
30. De Boni U, Crapper DR (1978) Paired helical filaments of the Alzheimer type in cultured neurones. Nature 271:566–568
    Article PubMed Google Scholar
31. de Calignon A, Polydoro M, Suarez-Calvet M, William C, Adamowicz DH, Kopeikina KJ, Pitstick R, Sahara N, Ashe KH, Carlson GA, Spires-Jones TL, Hyman BT (2012) Propagation of tau pathology in a model of early Alzheimer’s disease. Neuron 73:685–697. doi:10.1016/j.neuron.2011.11.033
    Article PubMed PubMed Central CAS Google Scholar
32. de Silva R, Lashley T, Strand C, Shiarli AM, Shi J, Tian J, Bailey KL, Davies P, Bigio EH, Arima K, Iseki E, Murayama S, Kretzschmar H, Neumann M, Lippa C, Halliday G, MacKenzie J, Ravid R, Dickson D, Wszolek Z, Iwatsubo T, Pickering-Brown SM, Holton J, Lees A, Revesz T, Mann DM (2006) An immunohistochemical study of cases of sporadic and inherited frontotemporal lobar degeneration using 3R- and 4R-specific tau monoclonal antibodies. Acta Neuropathol 111:329–340. doi:10.1007/s00401-006-0048-x
    Article PubMed Google Scholar
33. Dickson DW, Kouri N, Murray ME, Josephs KA (2011) Neuropathology of frontotemporal lobar degeneration-tau (FTLD-tau). J Mol Neurosci 45:384–389. doi:10.1007/s12031-011-9589-0
    Article PubMed PubMed Central CAS Google Scholar
34. Dinkel PD, Siddiqua A, Huynh H, Shah M, Margittai M (2011) Variations in filament conformation dictate seeding barrier between three- and four-repeat tau. Biochemistry 50:4330–4336. doi:10.1021/bi2004685
    Article PubMed CAS Google Scholar
35. Falcon B, Cavallini A, Angers R, Glover S, Murray TK, Barnham L, Jackson S, O’Neill MJ, Isaacs AM, Hutton ML, Szekeres PG, Goedert M, Bose S (2015) Conformation determines the seeding potencies of native and recombinant Tau aggregates. J Biol Chem 290:1049–1065. doi:10.1074/jbc.M114.589309
    Article PubMed PubMed Central CAS Google Scholar
36. Frost B, Diamond MI (2010) Prion-like mechanisms in neurodegenerative diseases. Nat Rev Neurosci 11:155–159. doi:10.1038/nrn2786
    PubMed PubMed Central CAS Google Scholar
37. Frost B, Jacks RL, Diamond MI (2009) Propagation of tau misfolding from the outside to the inside of a cell. J Biol Chem 284:12845–12852. doi:10.1074/jbc.M808759200
    Article PubMed PubMed Central CAS Google Scholar
38. Gajdusek DC (1994) Nucleation of amyloidogenesis in infectious and noninfectious amyloidoses of brain. Ann N Y Acad Sci 724:173–190
    Article PubMed CAS Google Scholar
39. Gardner RC, Boxer AL, Trujillo A, Mirsky JB, Guo CC, Gennatas ED, Heuer HW, Fine E, Zhou J, Kramer JH, Miller BL, Seeley WW (2013) Intrinsic connectivity network disruption in progressive supranuclear palsy. Ann Neurol 73:603–616. doi:10.1002/ana.23844
    Article PubMed PubMed Central Google Scholar
40. Gerson JE, Sengupta U, Lasagna-Reeves CA, Guerrero-Munoz MJ, Troncoso J, Kayed R (2014) Characterization of tau oligomeric seeds in progressive supranuclear palsy. Acta Neuropathol Commun 2:73. doi:10.1186/2051-5960-2-73
    Article PubMed PubMed Central Google Scholar
41. Ghetti B, Tagliavini F, Giaccone G, Bugiani O, Frangione B, Farlow MR, Dlouhy SR (1994) Familial Gerstmann-Sträussler-Scheinker disease with neurofibrillary tangles. Mol Neurobiol 8:41–48. doi:10.1007/BF02778006
    Article PubMed CAS Google Scholar
42. Goedert M, Spillantini MG, Potier MC, Ulrich J, Crowther RA (1989) Cloning and sequencing of the cDNA encoding an isoform of microtubule-associated protein tau containing four tandem repeats: differential expression of tau protein mRNAs in human brain. EMBO J 8:393–399
    PubMed PubMed Central CAS Google Scholar
43. Gotz J, Chen F, van Dorpe J, Nitsch RM (2001) Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils. Science 293:1491–1495. doi:10.1126/science.1062097
    Article PubMed CAS Google Scholar
44. Grudzien A, Shaw P, Weintraub S, Bigio E, Mash DC, Mesulam MM (2007) Locus coeruleus neurofibrillary degeneration in aging, mild cognitive impairment and early Alzheimer’s disease. Neurobiol Aging 28:327–335. doi:10.1016/j.neurobiolaging.2006.02.007
    Article PubMed CAS Google Scholar
45. Grundke-Iqbal I, Iqbal K, Quinlan M, Tung YC, Zaidi MS, Wisniewski HM (1986) Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J Biol Chem 261:6084–6089
    PubMed CAS Google Scholar
46. Guo JL, Lee VM (2011) Seeding of normal Tau by pathological Tau conformers drives pathogenesis of Alzheimer-like tangles. J Biol Chem 286:15317–15331. doi:10.1074/jbc.M110.209296
    Article PubMed PubMed Central CAS Google Scholar
47. Harbi D, Harrison PM (2014) Classifying prion and prion-like phenomena. Prion 8(2) (pii: 27960)
48. Harris JA, Koyama A, Maeda S, Ho K, Devidze N, Dubal DB, Yu GQ, Masliah E, Mucke L (2012) Human P301L-mutant tau expression in mouse entorhinal-hippocampal network causes tau aggregation and presynaptic pathology but no cognitive deficits. PLoS One 7:e45881. doi:10.1371/journal.pone.0045881
    Article PubMed PubMed Central CAS Google Scholar
49. Hirano A, Zimmerman HM (1962) Alzheimer’s neurofibrillary changes. A topographic study. Arch Neurol 7:227–242
    Article PubMed CAS Google Scholar
50. Holmes BB, DeVos SL, Kfoury N, Li M, Jacks R, Yanamandra K, Ouidja MO, Brodsky FM, Marasa J, Bagchi DP, Kotzbauer PT, Miller TM, Papy-Garcia D, Diamond MI (2013) Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds. Proc Natl Acad Sci USA 110:E3138–E3147. doi:10.1073/pnas.1301440110
    Article PubMed PubMed Central CAS Google Scholar
51. Holmes BB, Furman JL, Mahan TE, Yamasaki TR, Mirbaha H, Eades WC, Belaygorod L, Cairns NJ, Holtzman DM, Diamond MI (2014) Proteopathic tau seeding predicts tauopathy in vivo. Proc Natl Acad Sci USA 111:E4376–E4385. doi:10.1073/pnas.1411649111
    Article PubMed PubMed Central CAS Google Scholar
52. Hutton M, Lendon CL, Rizzu P, Baker M, Froelich S, Houlden H, Pickering-Brown S, Chakraverty S, Isaacs A, Grover A, Hackett J, Adamson J, Lincoln S, Dickson D, Davies P, Petersen RC, Stevens M, de Graaff E, Wauters E, van Baren J, Hillebrand M, Joosse M, Kwon JM, Nowotny P, Che LK, Norton J, Morris JC, Reed LA, Trojanowski J, Basun H, Lannfelt L, Neystat M, Fahn S, Dark F, Tannenberg T, Dodd PR, Hayward N, Kwok JB, Schofield PR, Andreadis A, Snowden J, Craufurd D, Neary D, Owen F, Oostra BA, Hardy J, Goate A, van Swieten J, Mann D, Lynch T, Heutink P (1998) Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393:702–705. doi:10.1038/31508
    Article PubMed CAS Google Scholar
53. Iba M, Guo JL, McBride JD, Zhang B, Trojanowski JQ, Lee VM (2013) Synthetic tau fibrils mediate transmission of neurofibrillary tangles in a transgenic mouse model of Alzheimer’s-like tauopathy. J Neurosci 33:1024–1037. doi:10.1523/JNEUROSCI.2642-12.2013
    Article PubMed PubMed Central CAS Google Scholar
54. Iqbal K, Grundke-Iqbal I, Zaidi T, Merz PA, Wen GY, Shaikh SS, Wisniewski HM, Alafuzoff I, Winblad B (1986) Defective brain microtubule assembly in Alzheimer’s disease. Lancet 2:421–426 (pii: S0140-6736(86)92134-3)
    Article PubMed CAS Google Scholar
55. Irwin DJ, Abrams JY, Schonberger LB, Leschek EW, Mills JL, Lee VM, Trojanowski JQ (2013) Evaluation of potential infectivity of Alzheimer and Parkinson disease proteins in recipients of cadaver-derived human growth hormone. JAMA Neurol 70:462–468. doi:10.1001/jamaneurol.2013.1933
    Article PubMed PubMed Central Google Scholar
56. Jarero-Basulto JJ, Luna-Munoz J, Mena R, Kristofikova Z, Ripova D, Perry G, Binder LI, Garcia-Sierra F (2013) Proteolytic cleavage of polymeric tau protein by caspase-3: implications for Alzheimer disease. J Neuropathol Exp Neurol 72:1145–1161. doi:10.1097/NEN.0000000000000013
    Article PubMed CAS Google Scholar
57. Jellinger KA, Bancher C (1998) Senile dementia with tangles (tangle predominant form of senile dementia). Brain Pathol 8:367–376
    Article PubMed CAS Google Scholar
58. Josephs KA, Katsuse O, Beccano-Kelly DA, Lin WL, Uitti RJ, Fujino Y, Boeve BF, Hutton ML, Baker MC, Dickson DW (2006) Atypical progressive supranuclear palsy with corticospinal tract degeneration. J Neuropathol Exp Neurol 65:396–405. doi:10.1097/01.jnen.0000218446.38158.61
    Article PubMed Google Scholar
59. Kanmert D, Cantlon A, Muratore CR, Jin M, O’Malley TT, Lee G, Young-Pearse TL, Selkoe DJ, Walsh DM (2015) C-terminally truncated forms of tau, but not full-length tau or its C-terminal fragments, are released from neurons independently of cell death. J Neurosci 35:10851–10865. doi:10.1523/JNEUROSCI.0387-15.2015
    Article PubMed CAS Google Scholar
60. Kfoury N, Holmes BB, Jiang H, Holtzman DM, Diamond MI (2012) Trans-cellular propagation of Tau aggregation by fibrillar species. J Biol Chem 287:19440–19451. doi:10.1074/jbc.M112.346072
    Article PubMed PubMed Central CAS Google Scholar
61. Kosik KS (1993) The molecular and cellular biology of tau. Brain Pathol 3:39–43
    Article PubMed CAS Google Scholar
62. Lee G, Neve RL, Kosik KS (1989) The microtubule binding domain of tau protein. Neuron 2:1615–1624 (pii: 0896-6273(89)90050-0)
    Article PubMed CAS Google Scholar
63. Lee VM, Trojanowski JQ (1999) Neurodegenerative tauopathies: human disease and transgenic mouse models. Neuron 24:507–510 (pii: S0896-6273(00)81106-X)
    Article PubMed CAS Google Scholar
64. Lewis J, Dickson DW, Lin WL, Chisholm L, Corral A, Jones G, Yen SH, Sahara N, Skipper L, Yager D, Eckman C, Hardy J, Hutton M, McGowan E (2001) Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science 293:1487–1491. doi:10.1126/science.1058189
    Article PubMed CAS Google Scholar
65. Liu L, Drouet V, Wu JW, Witter MP, Small SA, Clelland C, Duff K (2012) Trans-synaptic spread of tau pathology in vivo. PLoS One 7:e31302. doi:10.1371/journal.pone.0031302
    Article PubMed PubMed Central CAS Google Scholar
66. Mesulam M, Shaw P, Mash D, Weintraub S (2004) Cholinergic nucleus basalis tauopathy emerges early in the aging-MCI-AD continuum. Ann Neurol 55:815–828. doi:10.1002/ana.20100
    Article PubMed CAS Google Scholar
67. Meyer V, Dinkel PD, Rickman Hager E, Margittai M (2014) Amplification of Tau fibrils from minute quantities of seeds. Biochemistry 53:5804–5809. doi:10.1021/bi501050g
    Article PubMed PubMed Central CAS Google Scholar
68. Michel CH, Kumar S, Pinotsi D, Tunnacliffe A, St George-Hyslop P, Mandelkow E, Mandelkow EM, Kaminski CF, Kaminski Schierle GS (2014) Extracellular monomeric tau protein is sufficient to initiate the spread of tau protein pathology. J Biol Chem 289:956–967. doi:10.1074/jbc.M113.515445
    Article PubMed PubMed Central CAS Google Scholar
69. Mirbaha H, Holmes BB, Sanders DW, Bieschke J, Diamond MI (2015) Tau trimers are the minimal propagation unit spontaneously internalized to seed intracellular aggregation. J Biol Chem 290:14893–14903. doi:10.1074/jbc.M115.652693
    Article PubMed CAS Google Scholar
70. Miyasaka T, Morishima-Kawashima M, Ravid R, Kamphorst W, Nagashima K, Ihara Y (2001) Selective deposition of mutant tau in the FTDP-17 brain affected by the P301L mutation. J Neuropathol Exp Neurol 60:872–884
    PubMed CAS Google Scholar
71. Mori H, Hosoda K, Matsubara E, Nakamoto T, Furiya Y, Endoh R, Usami M, Shoji M, Maruyama S, Hirai S (1995) Tau in cerebrospinal fluids: establishment of the sandwich ELISA with antibody specific to the repeat sequence in tau. Neurosci Lett 186:181–183
    Article PubMed CAS Google Scholar
72. Morozova OA, March ZM, Robinson AS, Colby DW (2013) Conformational features of tau fibrils from Alzheimer’s disease brain are faithfully propagated by unmodified recombinant protein. Biochemistry 52:6960–6967. doi:10.1021/bi400866w
    Article PubMed PubMed Central CAS Google Scholar
73. Murray ME, Graff-Radford NR, Ross OA, Petersen RC, Duara R, Dickson DW (2011) Neuropathologically defined subtypes of Alzheimer’s disease with distinct clinical characteristics: a retrospective study. Lancet Neurol 10:785–796. doi:10.1016/S1474-4422(11)70156-9
    Article PubMed PubMed Central Google Scholar
74. Nitsch RM, Rebeck GW, Deng M, Richardson UI, Tennis M, Schenk DB, Vigo-Pelfrey C, Lieberburg I, Wurtman RJ, Hyman BT et al (1995) Cerebrospinal fluid levels of amyloid beta-protein in Alzheimer’s disease: inverse correlation with severity of dementia and effect of apolipoprotein E genotype. Ann Neurol 37:512–518. doi:10.1002/ana.410370414
    Article PubMed CAS Google Scholar
75. Nonaka T, Watanabe ST, Iwatsubo T, Hasegawa M (2010) Seeded aggregation and toxicity of α-synuclein and tau: cellular models of neurodegenerative diseases. J Biol Chem 285:34885–34898. doi:10.1074/jbc.M110.148460
    Article PubMed PubMed Central CAS Google Scholar
76. Nubling G, Levin J, Bader B, Israel L, Botzel K, Lorenzl S, Giese A (2012) Limited cleavage of tau with matrix-metalloproteinase MMP-9, but not MMP-3, enhances tau oligomer formation. Exp Neurol 237:470–476. doi:10.1016/j.expneurol.2012.07.018
    Article PubMed CAS Google Scholar
77. O’Meara ES, Kukull WA, Schellenberg GD, Bowen JD, McCormick WC, Teri L, Pfanschmidt M, Thompson JD, Larson EB (1997) Alzheimer’s disease and history of blood transfusion by apolipoprotein-E genotype. Neuroepidemiology 16:86–93
    Article PubMed Google Scholar
78. On not eating your neighbor (1968). JAMA 206:1784–1785
79. Park SY, Ferreira A (2005) The generation of a 17 kDa neurotoxic fragment: an alternative mechanism by which tau mediates beta-amyloid-induced neurodegeneration. J Neurosci 25:5365–5375. doi:10.1523/JNEUROSCI.1125-05.2005
    Article PubMed PubMed Central CAS Google Scholar
80. Peeraer E, Bottelbergs A, Van Kolen K, Stancu IC, Vasconcelos B, Mahieu M, Duytschaever H, Ver Donck L, Torremans A, Sluydts E, Van Acker N, Kemp JA, Mercken M, Brunden KR, Trojanowski JQ, Dewachter I, Lee VM, Moechars D (2015) Intracerebral injection of preformed synthetic tau fibrils initiates widespread tauopathy and neuronal loss in the brains of tau transgenic mice. Neurobiol Dis 73:83–95. doi:10.1016/j.nbd.2014.08.032
    Article PubMed PubMed Central CAS Google Scholar
81. Polydoro M, de Calignon A, Suarez-Calvet M, Sanchez L, Kay KR, Nicholls SB, Roe AD, Pitstick R, Carlson GA, Gomez-Isla T, Spires-Jones TL, Hyman BT (2013) Reversal of neurofibrillary tangles and tau-associated phenotype in the rTgTauEC model of early Alzheimer’s disease. J Neurosci 33:13300–13311. doi:10.1523/JNEUROSCI.0881-13.2013
    Article PubMed PubMed Central CAS Google Scholar
82. Pooler AM, Polydoro M, Maury EA, Nicholls SB, Reddy SM, Wegmann S, William C, Saqran L, Cagsal-Getkin O, Pitstick R, Beier DR, Carlson GA, Spires-Jones TL, Hyman BT (2015) Amyloid accelerates tau propagation and toxicity in a model of early Alzheimer’s disease. Acta Neuropathol Commun 3:14. doi:10.1186/s40478-015-0199-x
    Article PubMed PubMed Central Google Scholar
83. Prusiner SB (1982) Novel proteinaceous infectious particles cause scrapie. Science 216:136–144
    Article PubMed CAS Google Scholar
84. Revesz T, Holton JL, Doshi B, Anderton BH, Scaravilli F, Plant GT (1999) Cytoskeletal pathology in familial cerebral amyloid angiopathy (British type) with non-neuritic amyloid plaque formation. Acta Neuropathol 97:170–176
    Article PubMed CAS Google Scholar
85. Rissman RA, Poon WW, Blurton-Jones M, Oddo S, Torp R, Vitek MP, LaFerla FM, Rohn TT, Cotman CW (2004) Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology. J Clin Invest 114:121–130. doi:10.1172/JCI20640
    Article PubMed PubMed Central CAS Google Scholar
86. Sanders DW, Kaufman SK, DeVos SL, Sharma AM, Mirbaha H, Li A, Barker SJ, Foley AC, Thorpe JR, Serpell LC, Miller TM, Grinberg LT, Seeley WW, Diamond MI (2014) Distinct tau prion strains propagate in cells and mice and define different tauopathies. Neuron 82:1271–1288. doi:10.1016/j.neuron.2014.04.047
    Article PubMed PubMed Central CAS Google Scholar
87. Santa-Maria I, Varghese M, Ksiezak-Reding H, Dzhun A, Wang J, Pasinetti GM (2012) Paired helical filaments from Alzheimer disease brain induce intracellular accumulation of Tau protein in aggresomes. J Biol Chem 287:20522–20533. doi:10.1074/jbc.M111.323279
    Article PubMed PubMed Central CAS Google Scholar
88. Santacruz K, Lewis J, Spires T, Paulson J, Kotilinek L, Ingelsson M, Guimaraes A, DeTure M, Ramsden M, McGowan E, Forster C, Yue M, Orne J, Janus C, Mariash A, Kuskowski M, Hyman BT, Hutton M, Ashe KH (2005) Tau suppression in a neurodegenerative mouse model improves memory function. Science 309:476–481
    Article PubMed PubMed Central CAS Google Scholar
89. Seeley WW, Crawford RK, Zhou J, Miller BL, Greicius MD (2009) Neurodegenerative diseases target large-scale human brain networks. Neuron 62:42–52. doi:10.1016/j.neuron.2009.03.024
    Article PubMed PubMed Central CAS Google Scholar
90. Sokolow S, Henkins KM, Bilousova T, Gonzalez B, Vinters HV, Miller CA, Cornwell L, Poon WW, Gylys KH (2015) Pre-synaptic C-terminal truncated tau is released from cortical synapses in Alzheimer’s disease. J Neurochem 133:368–379. doi:10.1111/jnc.12991
    Article PubMed CAS Google Scholar
91. Spillantini MG, Murrell JR, Goedert M, Farlow MR, Klug A, Ghetti B (1998) Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. Proc Natl Acad Sci USA 95:7737–7741
    Article PubMed PubMed Central CAS Google Scholar
92. Stancu IC, Vasconcelos B, Ris L, Wang P, Villers A, Peeraer E, Buist A, Terwel D, Baatsen P, Oyelami T, Pierrot N, Casteels C, Bormans G, Kienlen-Campard P, Octave JN, Moechars D, Dewachter I (2015) Templated misfolding of Tau by prion-like seeding along neuronal connections impairs neuronal network function and associated behavioral outcomes in Tau transgenic mice. Acta Neuropathol 129:875–894. doi:10.1007/s00401-015-1413-4
    Article PubMed PubMed Central CAS Google Scholar
93. Terwel D, Lasrado R, Snauwaert J, Vandeweert E, Van Haesendonck C, Borghgraef P, Van Leuven F (2005) Changed conformation of mutant Tau-P301L underlies the moribund tauopathy, absent in progressive, nonlethal axonopathy of Tau-4R/2N transgenic mice. J Biol Chem 280:3963–3973. doi:10.1074/jbc.M409876200
    Article PubMed CAS Google Scholar
94. Uchihara T, Mitani K, Mori H, Kondo H, Yamada M, Ikeda K (1994) Abnormal cytoskeletal pathology peculiar to corticobasal degeneration is different from that of Alzheimer’s disease or progressive supranuclear palsy. Acta Neuropathol 88:379–383
    Article PubMed CAS Google Scholar
95. Uchihara T, Nakamura A, Yamazaki M, Mori O, Ikeda K, Tsuchiya K (2001) Different conformation of neuronal tau deposits distinguished by double immunofluorescence with AT8 and thiazin red combined with Gallyas method. Acta Neuropathol 102:462–466
    PubMed CAS Google Scholar
96. Vandermeeren M, Mercken M, Vanmechelen E, Six J, van de Voorde A, Martin JJ, Cras P (1993) Detection of tau proteins in normal and Alzheimer’s disease cerebrospinal fluid with a sensitive sandwich enzyme-linked immunosorbent assay. J Neurochem 61:1828–1834
    Article PubMed CAS Google Scholar
97. Vigo-Pelfrey C, Seubert P, Barbour R, Blomquist C, Lee M, Lee D, Coria F, Chang L, Miller B, Lieberburg I et al (1995) Elevation of microtubule-associated protein tau in the cerebrospinal fluid of patients with Alzheimer’s disease. Neurology 45:788–793
    Article PubMed CAS Google Scholar
98. Wang Y, Garg S, Mandelkow EM, Mandelkow E (2010) Proteolytic processing of tau. Biochem Soc Trans 38:955–961. doi:10.1042/BST0380955
    Article PubMed CAS Google Scholar
99. Weaver CL, Espinoza M, Kress Y, Davies P (2000) Conformational change as one of the earliest alterations of tau in Alzheimer’s disease. Neurobiol Aging 21:719–727 (pii: S0197-4580(00)00157-3)
    Article PubMed CAS Google Scholar
100. Williams DR, Holton JL, Strand K, Revesz T, Lees AJ (2007) Pure akinesia with gait freezing: a third clinical phenotype of progressive supranuclear palsy. Mov Disord 22:2235–2241. doi:10.1002/mds.21698
     Article PubMed Google Scholar
101. Wolozin B, Davies P (1987) Alzheimer-related neuronal protein A68: specificity and distribution. Ann Neurol 22:521–526. doi:10.1002/ana.410220412
     Article PubMed CAS Google Scholar
102. Wu JW, Herman M, Liu L, Simoes S, Acker CM, Figueroa H, Steinberg JI, Margittai M, Kayed R, Zurzolo C, Di Paolo G, Duff KE (2013) Small misfolded Tau species are internalized via bulk endocytosis and anterogradely and retrogradely transported in neurons. J Biol Chem 288:1856–1870. doi:10.1074/jbc.M112.394528
     Article PubMed PubMed Central CAS Google Scholar
103. Yamada K, Cirrito JR, Stewart FR, Jiang H, Finn MB, Holmes BB, Binder LI, Mandelkow EM, Diamond MI, Lee VM, Holtzman DM (2011) In vivo microdialysis reveals age-dependent decrease of brain interstitial fluid tau levels in P301S human tau transgenic mice. J Neurosci 31:13110–13117. doi:10.1523/JNEUROSCI.2569-11.2011
     Article PubMed PubMed Central CAS Google Scholar
104. Yanamandra K, Kfoury N, Jiang H, Mahan TE, Ma S, Maloney SE, Wozniak DF, Diamond MI, Holtzman DM (2013) Anti-tau antibodies that block tau aggregate seeding in vitro markedly decrease pathology and improve cognition in vivo. Neuron 80:402–414. doi:10.1016/j.neuron.2013.07.046
     Article PubMed PubMed Central CAS Google Scholar
105. Yetman MJ, Lillehaug S, Bjaalie JG, Leergaard TB, Jankowsky JL (2015) Transgene expression in the Nop-tTA driver line is not inherently restricted to the entorhinal cortex. Brain Struct Funct. doi:10.1007/s00429-015-1040-9
     PubMed Google Scholar
106. Yoshiyama Y, Higuchi M, Zhang B, Huang SM, Iwata N, Saido TC, Maeda J, Suhara T, Trojanowski JQ, Lee VM (2007) Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53:337–351. doi:10.1016/j.neuron.2007.01.010
     Article PubMed CAS Google Scholar
107. Zhang Z, Song M, Liu X, Kang SS, Kwon IS, Duong DM, Seyfried NT, Hu WT, Liu Z, Wang JZ, Cheng L, Sun YE, Yu SP, Levey AI, Ye K (2014) Cleavage of tau by asparagine endopeptidase mediates the neurofibrillary pathology in Alzheimer’s disease. Nat Med 20:1254–1262. doi:10.1038/nm.3700
     Article PubMed PubMed Central CAS Google Scholar
108. Zhou J, Seeley WW (2014) Network dysfunction in Alzheimer’s disease and frontotemporal dementia: implications for psychiatry. Biol Psychiatry 75:565–573. doi:10.1016/j.biopsych.2014.01.020
     Article PubMed Google Scholar

Download references